Ameliorating effects of tropisetron on dopaminergic disruption of prepulse inhibition via the alpha(7) nicotinic acetylcholine receptor in Wistar rats

Brain Res. 2010 Sep 24;1353:152-8. doi: 10.1016/j.brainres.2010.07.037. Epub 2010 Jul 29.

Abstract

Nicotine has ameliorating effects on sensorimotor gating deficits in schizophrenia. We have shown that nicotine ameliorated disruption of prepulse inhibition (PPI) via the alpha(7) nicotinic acetylcholine receptor (nAChR) in Wistar rats. The 5-HT(3) receptor antagonist tropisetron was recently found to be an alpha(7) nAChR partial agonist. We initially investigated the effects of tropisetron on disruption of PPI induced by phencyclidine (PCP) (2mg/kg) or apomorphine (1mg/kg). Tropisetron had no effect on the disruption of PPI induced by PCP, but ameliorated the disruption by apomorphine. The ameliorating effect of tropisetron was antagonized by methyllycaconitine (2 or 5mg/kg), a partially selective alpha(7) nAChR antagonist. Next, to find the action site of tropisetron, we examined c-Fos protein expression in the nucleus accumbens (NAc), dorsolateral striatum (DLst) and ventral tegmental area (VTA). Tropisetron alone did not change the number of c-Fos-positive cells, whereas apomorphine increased the number of positive cells in the NAc and DLst. Tropisetron administration followed by apomorphine administration decreased the number of positive cells in the VTA compared with the apomorphine-alone group. These results suggest that tropisetron has an ameliorating effect on the sensorimotor gating deficits via the alpha(7) nAChR, and that one possible site of its action is the VTA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Acoustic Stimulation / adverse effects
  • Analysis of Variance
  • Animals
  • Apomorphine / pharmacology
  • Brain / drug effects
  • Brain / metabolism
  • Dopamine / metabolism*
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Indoles / pharmacology*
  • Inhibition, Psychological*
  • Male
  • Mecamylamine / pharmacology
  • Models, Biological
  • Nicotinic Antagonists / pharmacology
  • Ondansetron / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Psychoacoustics
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / metabolism*
  • Reflex, Startle / drug effects*
  • Reflex, Startle / physiology
  • Serotonin Antagonists / pharmacology*
  • Stereotyped Behavior / drug effects
  • Tropisetron
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, rat
  • Dopamine Agonists
  • Indoles
  • Nicotinic Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, Nicotinic
  • Serotonin Antagonists
  • alpha7 Nicotinic Acetylcholine Receptor
  • methyllycaconitine
  • Ondansetron
  • Mecamylamine
  • Tropisetron
  • Apomorphine
  • Dopamine
  • Aconitine